Transplantation of autologous retinal pigment epithelium in eyes with foveal neovascularization resulting from age-related macular degeneration: a pilot study

Binder, Susanne; Stolba, U.; Krebs, Ilse; Kellner, Lukas; Jahn, C.; Feichtinger, Hans G.; Povelka, Margit; Frohner, Ursula; Krüger, Andreas; Hilgers, Ralf-Dieter; Krugluger, Walter

doi:10.1016/s0002-9394(01)01373-3

Cited by 187 publications

(121 citation statements)

References 32 publications

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“…However, there is a lack of demonstrable presence or function of these transplants in patients [4,5,23]. Peyman et al first reported the translocation of a free full-thickness autologous graft consisting of RPE, Bruch's membrane, choriocapillaris and choroid taken from the paramacular region in one patient [29].…”

Section: Introductionmentioning

confidence: 99%

Retinal pigment epithelium and choroid translocation in patients with exudative age-related macular degeneration: long-term results

Maaijwee

Heimann

Missotten

et al. 2007

Graefes Arch Clin Exp Ophthalmol

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Background To study the results of the translocation of a free autologous retinal pigment epithelium (RPE)-choroid graft after removal of a subfoveal choroidal neovascular membrane in patients with exudative age-related macular degeneration (AMD), and to determine whether preoperative variables may predict visual outcome at 1 year after surgery. Methods Prospective interventional case series of 84 eyes of 83 consecutive eligible patients with exudative AMD with a minimal follow-up of 1 year after surgery. Of this group, 45, 24 and 11 patients reached a follow-up of respectively 2, 3 and 4 years. Pre-and postoperative evaluation included ETDRS visual acuity (VA), fixation testing and color fundus photography. Preoperative fluorescein angiograms were assessed by masked readers for lesion size, size of hemorrhage and lesion composition according to the MPS criteria. The relationship between lesion composition adjusted for preoperative delay and VA, lesion size, percentage of blood, and visual outcome at 1 year after surgery was analyzed. Results The mean VA (logMAR) improved slightly at 1 and 2 years (0.89, Δ=−0.06), 3 years (0.79, Δ=−0.16) and 4 years (0.74, Δ=−0.21) after surgery. Five patients had a preoperative VA better than 20/80, compared to 19 out of 84, six out of 45, four out of 24 and two out of 11 after 1, 2, 3 and 4 years respectively. Fixation was located on the graft in 62 patients (74%) up to the last examination. Predominantly classic and occult lesions had a significant better prognosis than minimally classic or hemorrhagic (≥50% blood) lesions. Retinal detachment occurred in seven patients; two caused by rhegmatogenous detachment and five caused by proliferative vitreoretinopathy. In 11 eyes, a recurrent or persisting neovascular membrane was observed. Conclusion An autologous free RPE-choroid graft may stabilize or improve vision in patients with exudative AMD up to 4 years after surgery.

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Section: Introductionmentioning

confidence: 99%

Retinal pigment epithelium and choroid translocation in patients with exudative age-related macular degeneration: long-term results

Maaijwee

Heimann

Missotten

et al. 2007

Graefes Arch Clin Exp Ophthalmol

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“…Although no proven visually beneficial treatments for patients are currently available, a variety of approaches to preserve or restore vision are under investigation, including neural retinal transplantation (Kaplan et al, 1997;Algvere et al, 1999;Das et al, 1999;Radtke et al, 1999;Humayun et al, 2000;Binder et al, 2002;Radtke et al, 2002;Berger et al, 2003), gene therapy (Bennett et al, 1996(Bennett et al, , 1998Ali et al, 2000;Bennett, 2000;Vollrath et al, 2001), pharmacotherapies (Faktorovich et al, 1990;Li et al, 1998;Chong et al, 1999;Caffe et al, 2001) and visual prosthetic devices (Weiland et al, 1999;Humayun et al, 1999a;Margalit et al, 2002;Lakhanpal et al, 2003).…”

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confidence: 99%

Restoration of visual responses following transplantation of intact retinal sheets in rd mice

Arai

Thomas

Seiler

et al. 2004

Experimental Eye Research

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Purpose. To correlate the functional outcomes with histologic findings following transplantation of fetal retinal sheets in rd mice, and to investigate the mechanisms of visual function restoration.Methods. Twenty-one postnatal day 31 -38 rd/rd (C3H/HeJ) mice were transplanted in one eye with retinal sheets (1·0 £ 0·4 mm) obtained from embryonic day (E) 17 enhanced-green-fluorescent protein (eGFP) mice. Five mice underwent sham surgery without insertion of tissue. Four to five weeks after transplantation, visual responses to a light flash were recorded across the superior colliculus (SC) in seven eyes of seven transplanted mice that had clear corneas and lenses, and in all five sham surgery mice. Following the SC recording, the eyes were enucleated and processed for immunohistochemistry and examined using confocal microscopy.Results. In three out of the seven eyes (43%), positive responses were recorded in the SC in an area topographically corresponding to the placement of the transplant in the host retina. No responses were recorded in the untreated eyes of 5-week-old and 9-week-old rd/rd mice, and in the 9-week-old sham surgery mice. In contrast, visual responses were recorded over the entire SC in normal eyes. The response onset latencies of the 3 transplanted mice with responses were similar to those of normal control mice. The organization of the graft did not appear to correlate as expected with the electrophysiology results, as eyes with well-organized, laminated grafts showed no response whereas the three light-responsive eyes had rosetted or disorganized grafts. All three light-responsive eyes demonstrated much higher levels of recoverin immunoreactivity in the host retina overlying the graft compared with untreated age-matched rd/rd mice.Conclusion. Restoration of the SC visual response does not appear to depend on a well-organized transplant in the rd mouse. Increased recoverin-staining in the host retina in light-responsive animals suggested that host cone rescue was the likely mechanism of vision restoration in this transplant model. q

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“…73 To avoid rejection, autologous RPE grafts were instead used. 74,75 RPE, harvested from the nasal subretinal region, was dissociated and transplanted around the macular region. Significant improvement in multifocal electroretinography was reported after 1-3 months, despite lack of long-term visual acuity improvement.…”

Section: Rpe Cell Replacementmentioning

confidence: 99%

Induced Pluripotent Stem Cell Therapies for Degenerative Disease of the Outer Retina: Disease Modeling and Cell Replacement

Foggia

Makwana

Ali³

et al. 2016

Journal of Ocular Pharmacology and Therapeutics

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Stem cell therapies are being explored as potential treatments for retinal disease. How to replace neurons in a degenerated retina presents a continued challenge for the regenerative medicine field that, if achieved, could restore sight. The major issues are: (i) the source and availability of donor cells for transplantation; (ii) the differentiation of stem cells into the required retinal cells; and (iii) the delivery, integration, functionality, and survival of new cells in the host neural network. This review considers the use of induced pluripotent stem cells (iPSC), currently under intense investigation, as a platform for cell transplantation therapy. Moreover, patientspecific iPSC are being developed for autologous cell transplantation and as a tool for modeling specific retinal diseases, testing gene therapies, and drug screening.

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Transplantation of autologous retinal pigment epithelium in eyes with foveal neovascularization resulting from age-related macular degeneration: a pilot study

Cited by 187 publications

References 32 publications

Retinal pigment epithelium and choroid translocation in patients with exudative age-related macular degeneration: long-term results

Retinal pigment epithelium and choroid translocation in patients with exudative age-related macular degeneration: long-term results

Restoration of visual responses following transplantation of intact retinal sheets in rd mice

Induced Pluripotent Stem Cell Therapies for Degenerative Disease of the Outer Retina: Disease Modeling and Cell Replacement

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